tbuckley/cabot-search huggingface dataset:
Genomic analysis of the international high-risk clonal lineage Klebsiella pneumoniae sequence type 395
Authors: Elvira R. Shaidullina, Michael Schwabe, Thomas Rohde, Valeria V. Shapovalova, Marina S. Dyachkova, Alina D. Matsvay, Yuliya A. Savochkina, Andrey A. Shelenkov, Yulia V. Mikhaylova, Katharina Sydow, François Lebreton, Evgeny A. Idelevich, Stefan E. Heiden, Karsten Becker, Roman S. Kozlov, German A. Shipulin, Vasiliy G. Akimkin, Michael Lalk, Sebastian Guenther, Andreas E. Zautner, Jürgen A. Bohnert, Ayslu M. Mardanova, Ruth Bouganim, Dror Marchaim, Katharina J. Hoff, Katharina Schaufler, Mikhail V. Edelstein
Journal: Genome Medicine (2023)

Klebsiella pneumoniae, which is frequently associated with hospital- and community-acquired infections, contains multidrug-resistant (MDR), hypervirulent (hv), non-MDR/non-hv as well as convergent representatives. It is known that mostly international high-risk clonal lineages including sequence types (ST) 11, 147, 258, and 307 drive their global spread. ST395, which was first reported in the context of a carbapenemase-associated outbreak in France in 2010, is a less well-characterized, yet emerging clonal lineage.
H3.3 contributes to chromatin accessibility and transcription factor binding at promoter-proximal regulatory elements in embryonic stem cells
Authors: Amanuel Tafessu, Ryan O’Hara, Sara Martire, Altair L. Dube, Purbita Saha, Vincent U. Gant, Laura A. Banaszynski
Journal: Genome biology (2023)

The histone variant H3.3 is enriched at active regulatory elements such as promoters and enhancers in mammalian genomes. These regions are highly accessible, creating an environment that is permissive to transcription factor binding and the recruitment of transcriptional coactivators that establish a unique chromatin post-translational landscape. How H3.3 contributes to the establishment and function of chromatin states at these regions is poorly understood.We perform genomic analyses of features associated with active promoter chromatin in mouse embryonic stem cells (ESCs) and find evidence of subtle yet widespread promoter dysregulation in the absence of H3.3. Loss of H3.3 results in reduced chromatin accessibility and transcription factor (TF) binding at promoters of expressed genes in ESCs. Likewise, enrichment of the transcriptional coactivator p300 and downstream histone H3 acetylation at lysine 27 (H3K27ac) is reduced at promoters in the absence of H3.3, along with reduced enrichment of the acetyl lysine reader BRD4. Despite the observed chromatin dysregulation, H3.3 KO ESCs maintain transcription from ESC-specific genes. However, upon undirected differentiation, H3.3 KO cells retain footprinting of ESC-specific TF motifs and fail to generate footprints of lineage-specific TF motifs, in line with their diminished capacity to differentiate.H3.3 facilitates DNA accessibility, transcription factor binding, and histone post-translational modification at active promoters. While H3.3 is not required for maintaining transcription in ESCs, it does promote de novo transcription factor binding which may contribute to the dysregulation of cellular differentiation in the absence of H3.3.
RNA Methylome Reveals the m<b>6</b>A-Mediated Regulation of Flavor Metabolites in Tea Leaves under Solar-Withering
Authors: Chen Zhu, Shuting Zhang, Chengzhe Zhou, Caiyun Tian, Biying Shi, Kai Xu, Linjie Huang, Yun Sun, Yuling Lin, Zhongxiong Lai, Yuqiong Guo
Journal: Genomics Proteomics & Bioinformatics (2023)

The epitranscriptomic mark N
An elusive consensus definition of sarcopenia impedes research and clinical treatment: A narrative review
Authors: Giulia Coletta, Stuart M. Phillips
Journal: Ageing Research Reviews (2023)

The definition of sarcopenia, the age-related loss of muscle mass, has evolved since the term's inception and yet there is no consensus. Many of the identified definitions of sarcopenia centre their criteria around the loss of muscle mass, loss of function, and weakness. Common variables to various definitions of sarcopenia are appendicular lean soft tissue mass (often called muscle mass), grip strength, and gait speed. However, a lack of consensus remains among operational definitions and diagnostics for this newly recognized disease and may be attributed to the absence of appropriate tools that accurately measure the outcomes of interest, such as skeletal muscle instead of lean mass. In this narrative review, we describe the evolution of the consensus groups' definition of sarcopenia, address the need for more accurate measures of muscle mass and function, and effective, low-cost treatments (i.e., resistance training and diet) for this disease. Consensus on what constitutes sarcopenia is critical to propel research in the field and, importantly, provide what prognostic value a sarcopenia diagnosis provides and how such a patient would be treated.
Epidemiology of Gastric Malignancies 2000–2018 According to Histology: A Population-Based Analysis of Incidence and Temporal Trends
Authors: Sheila D. Rustgi, Meg McKinley, Brandon McBay, Haley M. Zylberberg, Scarlett L. Gomez, Chin Hur, Fay Kastrinos, Samir Gupta, Michelle Kang Kim, Steven H. Itzkowitz, Shailja C. Shah
Journal: Clinical Gastroenterology and Hepatology (2023)
Late gadolinium enhancement and the risk of ventricular arrhythmias and sudden death in <scp>NYHA</scp> class I patients with non‐ischaemic cardiomyopathy
Authors: Andrea Di Marco, Pamela Brown, Gemma Mateus, Valentina Faga, Gaetano Nucifora, Eduard Claver, Jisela Viedma, Francisco Galvan, Joshua Bradley, Paolo D. Dallaglio, Fernando de Frutos, Christopher A. Miller, Josep Comín‐Colet, Ignasi Anguera, Matthias Schmitt
Journal: European Journal of Heart Failure (2023)
Bone status in men with heart failure: results from the Studies Investigating Co‐morbidities Aggravating Heart Failure
Authors: Goran Loncar, Tania Garfias‐Veitl, Miroslava Valentova, Mirela Vatic, Mitja Lainscak, Danilo Obradović, Thomas Bernd Dschietzig, Wolfram Doehner, Ewa A. Jankowska, Stefan D. Anker, Stephan von Haehling
Journal: European Journal of Heart Failure (2023)

To assess bone status expressed as hip bone mineral density (BMD) in men with heart failure (HF).A total of 141 male patients with HF underwent dual energy X-ray absorptiometry to assess their BMD. We analysed markers of bone metabolism. Patients were classified as lower versus higher BMD according to the median hip BMD (median = 1.162 g/cm2 ). Survival was assessed over 8 years of follow-up. Patients with lower BMD were older (71 ± 10 vs. 66 ± 9 years, p = 0.004), more likely to be sarcopenic (37% vs. 7%, p < 0.001) and to have lower peak oxygen consumption (absolute peak VO2 1373 ± 480 vs. 1676 ± 447 ml/min, p < 0.001), had higher osteoprotegerin and osteocalcin levels (both p < 0.05) compared to patients with higher BMD. Among 47 patients with repeated BMD assessments, a significant reduction in BMD was noted over 30 months of follow-up. In multivariate logistic regression analysis, serum osteocalcin remained independently related with lower BMD (odds ratio [OR] 1.738, 95% confidence interval [CI] 1.136-2.660, p = 0.011). Hip BMD and serum osteoprotegerin were independent predictors of impaired survival on Cox proportional hazard analysis (hazard ratio [HR] 0.069, 95% CI 0.011-0.444, p = 0.005, and HR 0.638, 95% CI 0.472-0.864, p = 0.004, respectively).Patients with HF lose BMD over time. Markers of bone turnover can help in identifying patients at risk with osteocalcin being an independent marker of lower hip BMD and osteoprotegerin an independent predictor of death. HF patients with increased osteocalcin and osteoprotegerin may benefit from BMD assessment as manifest osteoporosis seems to be too late for clinically meaningful intervention in HF.
Use of mechanical circulatory support in patients with non‐ischaemic cardiogenic shock
Authors: Benedikt Schrage, Jonas Sundermeyer, Benedikt Norbert Beer, Letizia Bertoldi, Alexander Bernhardt, Stefan Blankenberg, Jeroen Dauw, Zouhir Dindane, Dennis Eckner, Ingo Eitel, Tobias Graf, Patrick Horn, Paulus Kirchhof, Stefan Kluge, Axel Linke, Ulf Landmesser, Peter Luedike, Enzo Lüsebrink, Norman Mangner, Octavian Maniuc, Sven Möbius Winkler, Peter Nordbeck, Martin Orban, Federico Pappalardo, Matthias Pauschinger, Michal Pazdernik, Alastair Proudfoot, Matthew Kelham, Tienush Rassaf, Hermann Reichenspurner, Clemens Scherer, Paul Christian Schulze, Robert H.G. Schwinger, Carsten Skurk, Marek Sramko, Guido Tavazzi, Holger Thiele, Luca Villanova, Nuccia Morici, Antonia Wechsler, Ralf Westenfeld, Ephraim Winzer, Dirk Westermann
Journal: European Journal of Heart Failure (2023)

Despite its high incidence and mortality risk, there is no evidence-based treatment for non-ischaemic cardiogenic shock (CS). The aim of this study was to evaluate the use of mechanical circulatory support (MCS) for non-ischaemic CS treatment.In this multicentre, international, retrospective study, data from 890 patients with non-ischaemic CS, defined as CS due to severe de-novo or acute-on-chronic heart failure with no need for urgent revascularization, treated with or without active MCS, were collected. The association between active MCS use and the primary endpoint of 30-day mortality was assessed in a 1:1 propensity-matched cohort. MCS was used in 386 (43%) patients. Patients treated with MCS presented with more severe CS (37% vs. 23% deteriorating CS, 30% vs. 25% in extremis CS) and had a lower left ventricular ejection fraction at baseline (21% vs. 25%). After matching, 267 patients treated with MCS were compared with 267 patients treated without MCS. In the matched cohort, MCS use was associated with a lower 30-day mortality (hazard ratio 0.76, 95% confidence interval 0.59-0.97). This finding was consistent through all tested subgroups except when CS severity was considered, indicating risk reduction especially in patients with deteriorating CS. However, complications occurred more frequently in patients with MCS; e.g. severe bleeding (16.5% vs. 6.4%) and access-site related ischaemia (6.7% vs. 0%).In patients with non-ischaemic CS, MCS use was associated with lower 30-day mortality as compared to medical therapy only, but also with more complications. Randomized trials are needed to validate these findings.
Use of and association between heart failure pharmacological treatments and outcomes in obese versus non‐obese patients with heart failure with reduced ejection fraction: data from the Swedish Heart Failure Registry
Authors: Chiara Cappelletto, Davide Stolfo, Nicola Orsini, Lina Benson, Daniele Rodolico, Giuseppe M.C. Rosano, Ulf Dahlström, Gianfranco Sinagra, Lars H. Lund, Gianluigi Savarese
Journal: European Journal of Heart Failure (2023)

To investigate the use of guideline-directed medical therapies (GDMT) and associated outcomes in obese (body mass index ≥30 kg/m2 ) versus non-obese patients with heart failure (HF) with reduced ejection fraction (HFrEF).Patients with HFrEF from the Swedish HF Registry were included. Of 16 116 patients, 24% were obese. In obese versus non-obese patients, use of treatments was 91% versus 86% for renin-angiotensin system inhibitors (RASi)/angiotensin receptor-neprilysin inhibitors (ARNi), 94% versus 91% for beta-blockers, 53% versus 43% for mineralocorticoid receptor antagonists. Obesity was shown to be independently associated with more likely use of each treatment, triple combination therapy, and the achievement of target dose by multivariable logistic regressions. Multivariable Cox regressions showed use of RASi/ARNi and beta-blockers being independently associated with lower risk of all-cause/cardiovascular death regardless of obesity, although, when considering competing risks, a lower risk of cardiovascular death with RASi/ARNi in obese versus non-obese patients was observed. RASi/ARNi were associated with lower risk of HF hospitalization in obese but not in non-obese patients, whereas beta-blockers were not associated with the risk of HF hospitalization regardless of obesity. At the competing risk analysis, RASi/ARNi use was associated with higher risk of HF hospitalization regardless of obesity.Obese patients were more likely to receive optimal treatments after adjustment for factors affecting tolerability, suggesting that perceived beyond actual tolerance issues limit GDMT implementation. RASi/ARNi and beta-blockers were associated with lower mortality regardless of obesity, with a greater association between RASi/ARNi and lower cardiovascular death in obese versus non-obese patients when considering competing risk.
The impact of diabetic nephropathy and severe diabetic retinopathy on chronic limb threatening ischemia risk in individuals with type 1 diabetes: a nationwide, population study
Authors: Valma Harjutsalo, Milla Kallio, Carol Forsblom, Per-Henrik Groop
Journal: The Lancet Regional Health - Europe (2023)

The prevalence, incidence and risk factors and especially the effect of diabetic nephropathy (DN) and diabetic retinopathy on the risk of chronic limb threatening ischemia (CLTI) have been sparsely studied in individuals with type 1 diabetes (T1D). The prospective cohort study consisted of 4697 individuals with T1D from the nationwide Finnish Diabetic Nephropathy (FinnDiane) Study. Medical records were thoroughly reviewed in order to ascertain all CLTI events. The key risk factors were DN and severe diabetic retinopathy (SDR). There were 319 events of confirmed CLTI, 102 prevalent events at baseline and 217 incident events during the follow-up of 11.9 (IQR 9.3–13.8) years. The 12-year cumulative incidence of CLTI was 4.6% (95% CI 4.0–5.3). Risk factors included presence of DN, SDR, age, duration of diabetes, HbA1c, systolic blood pressure, triglycerides and current smoking. Sub-hazard ratios (SHRs) according to combinations of DN status and presence (+) or absence (−) of SDR were 4.8 (2.0–11.7) for normoalbuminuria/SDR+, 3.2 (1.1–9.4) for microalbuminuria/SDR−, 11.9 (5.4–26.5) for microalbuminuria/SDR+, 8.7 (3.2–23.2) for macroalbuminuria/SDR−, 15.6 (7.4–33.0) for macroalbuminuria/SDR+ and 37.9 (17.2–78.9) for kidney failure compared with individuals with normal albumin excretion rate and without SDR. Diabetic nephropathy, especially kidney failure, is associated with high risk of limb threatening ischemia in individuals with T1D. The risk of CLTI increases gradually according to the severity of diabetic nephropathy. Also, diabetic retinopathy is independently and additively associated with high risk of CLTI. This research was funded by grants from Folkhälsan Research Foundation, Academy of Finland (316664), Wilhelm and Else Stockmann Foundation, Liv och Hälsa Society, Novo Nordisk Foundation (NNF OC0013659), Finnish Foundation for Cardiovascular Research, Finnish Diabetes Research Foundation, Medical Society of Finland, Sigrid Jusélius Foundation and Helsinki University Hospital Research Funds.
Non-invasive transcranial volumetric ultrasound localization microscopy of the rat brain with continuous, high volume-rate acquisition
Authors: Jacob R. McCall, Francisco Santibanez, Hatim Belgharbi, Gianmarco F. Pinton, Paul A. Dayton
Journal: Theranostics (2023)

Rationale: Structure and function of the microvasculature provides critical information about disease state, can be used to identify local regions of pathology, and has been shown to be an indicator of response to therapy. Improved methods of assessing the microvasculature with non-invasive imaging modalities such as ultrasound will have an impact in biomedical theranostics. Ultrasound localization microscopy (ULM) is a new technology which allows processing of ultrasound data for visualization of microvasculature at a resolution better than allowed by acoustic diffraction with traditional ultrasound systems. Previous application of this modality in brain imaging has required the use of invasive procedures, such as a craniotomy, skull-thinning, or scalp removal, all of which are not feasible for the purpose of longitudinal studies. Methods: The impact of ultrasound localization microscopy is expanded using a 1024 channel matrix array ultrasonic transducer, four synchronized programmable ultrasound systems with customized high-performance hardware and software, and high-performance GPUs for processing. The potential of the imaging hardware and processing approaches are demonstrated in-vivo. Results: Our unique implementation allows asynchronous acquisition and data transfer for uninterrupted data collection at an ultra-high fixed frame rate. Using these methods, the vasculature was imaged using 100,000 volumes continuously at a volume acquisition rate of 500 volumes per second. With ULM, we achieved a resolution of 31 µm, which is a resolution improvement on conventional ultrasound imaging by nearly a factor of ten, in 3-D. This was accomplished while imaging through the intact skull with no scalp removal, which demonstrates the utility of this method for longitudinal studies. Conclusions: The results demonstrate new capabilities to rapidly image and analyze complex vascular networks in 3-D volume space for structural and functional imaging in disease assessment, targeted therapeutic delivery, monitoring response to therapy, and other theranostic applications.
Artificial Intelligence for diagnosing neoplasia on digital cholangioscopy: development and multicentric validation of a convolutional neural network model
Authors: Carlos Robles-Medranda, Jorge Baquerizo-Burgos, Juan Alcivar-Vasquez, Michel Kahaleh, Isaac Raijman, Rastislav Kunda, Miguel Puga-Tejada, Maria Egas-Izquierdo, Martha Arevalo-Mora, Juan C. Mendez, Amy Tyberg, Avik Sarkar, Haroon Shahid, Raquel del Valle-Zavala, Jorge Rodriguez, Ruxandra C. Merfea, Jonathan Barreto-Perez, Gabriela Saldaña-Pazmiño, Daniel Calle-Loffredo, Haydee Alvarado, Hannah P. Lukashok
Journal: Endoscopy (2023)

We aimed to develop a convolutional neural network (CNN) model for detecting neoplastic lesions during real-time digital single-operator cholangioscopy (DSOC) and to clinically validate the model through comparisons with DSOC expert and nonexpert endoscopists.In this two-stage study, we first developed and validated CNN1. Then, we performed a multicenter diagnostic trial to compare four DSOC experts and nonexperts against an improved model (CNN2). Lesions were classified into neoplastic and non-neoplastic in accordance with Carlos Robles-Medranda (CRM) and Mendoza disaggregated criteria. The final diagnosis of neoplasia was based on histopathology and 12-month follow-up outcomes.In stage I, CNN2 achieved a mean average precision of 0.88, an intersection over the union value of 83.24 %, and a total loss of 0.0975. For clinical validation, a total of 170 videos from newly included patients were analyzed with the CNN2. Half of cases (50 %) had neoplastic lesions. This model achieved significant accuracy values for neoplastic diagnosis, with a 90.5 % sensitivity, 68.2 % specificity, and 74.0 % and 87.8 % positive and negative predictive values, respectively. The CNN2 model outperformed nonexpert #2 (area under the receiver operating characteristic curve [AUC]-CRM 0.657 vs. AUC-CNN2 0.794, P < 0.05; AUC-Mendoza 0.582 vs. AUC-CNN2 0.794, P < 0.05), nonexpert #4 (AUC-CRM 0.683 vs. AUC-CNN2 0.791, P < 0.05), and expert #4 (AUC-CRM 0.755 vs. AUC-CNN2 0.848, P < 0.05; AUC-Mendoza 0.753 vs. AUC-CNN2 0.848, P < 0.05).The proposed CNN model distinguished neoplastic bile duct lesions with good accuracy and outperformed two nonexpert and one expert endoscopist.
Emerging roles of tRNA-derived fragments in cancer
Authors: Min Fu, Jianmei Gu, Maoye Wang, Jiahui Zhang, Yanke Chen, Pengcheng Jiang, Taofeng Zhu, Xu Zhang
Journal: Molecular Cancer (2023)

Abstract tRNA-derived fragments (tRFs) are an emerging category of small non-coding RNAs that are generated from cleavage of mature tRNAs or tRNA precursors. The advance in high-throughput sequencing has contributed to the identification of increasing number of tRFs with critical functions in distinct physiological and pathophysiological processes. tRFs can regulate cell viability, differentiation, and homeostasis through multiple mechanisms and are thus considered as critical regulators of human diseases including cancer. In addition, increasing evidence suggest the extracellular tRFs may be utilized as promising diagnostic and prognostic biomarkers for cancer liquid biopsy. In this review, we focus on the biogenesis, classification and modification of tRFs, and summarize the multifaceted functions of tRFs with an emphasis on the current research status and perspectives of tRFs in cancer.
BIGKnock: fine-mapping gene-based associations via knockoff analysis of biobank-scale data
Authors: Shiyang Ma, Chen Wang, Atlas Khan, Linxi Liu, James Dalgleish, Krzysztof Kiryluk, Zihuai He, Iuliana Ionita-Laza
Journal: Genome biology (2023)

We propose BIGKnock (BIobank-scale Gene-based association test via Knockoffs), a computationally efficient gene-based testing approach for biobank-scale data, that leverages long-range chromatin interaction data, and performs conditional genome-wide testing via knockoffs. BIGKnock can prioritize causal genes over proxy associations at a locus. We apply BIGKnock to the UK Biobank data with 405,296 participants for multiple binary and quantitative traits, and show that relative to conventional gene-based tests, BIGKnock produces smaller sets of significant genes that contain the causal gene(s) with high probability. We further illustrate its ability to pinpoint potential causal genes at [Formula: see text] of the associated loci.
Bayesian Machine Learning Enables Identification of Transcriptional Network Disruptions Associated with Drug-Resistant Prostate Cancer
Authors: Charles Blatti, Jesús de la Fuente, Huanyao Gao, Irene Marín-Goñi, Zikun Chen, Sihai D. Zhao, Winston Tan, Richard Weinshilboum, Krishna R. Kalari, Liewei Wang, Mikel Hernaez
Journal: Cancer Research (2023)

Abstract Survival rates of patients with metastatic castration-resistant prostate cancer (mCRPC) are low due to lack of response or acquired resistance to available therapies, such as abiraterone (Abi). A better understanding of the underlying molecular mechanisms is needed to identify effective targets to overcome resistance. Given the complexity of the transcriptional dynamics in cells, differential gene expression analysis of bulk transcriptomics data cannot provide sufficient detailed insights into resistance mechanisms. Incorporating network structures could overcome this limitation to provide a global and functional perspective of Abi resistance in mCRPC. Here, we developed TraRe, a computational method using sparse Bayesian models to examine phenotypically driven transcriptional mechanistic differences at three distinct levels: transcriptional networks, specific regulons, and individual transcription factors (TF). TraRe was applied to transcriptomic data from 46 patients with mCRPC with Abi-response clinical data and uncovered abrogated immune response transcriptional modules that showed strong differential regulation in Abi-responsive compared with Abi-resistant patients. These modules were replicated in an independent mCRPC study. Furthermore, key rewiring predictions and their associated TFs were experimentally validated in two prostate cancer cell lines with different Abi-resistance features. Among them, ELK3, MXD1, and MYB played a differential role in cell survival in Abi-sensitive and Abi-resistant cells. Moreover, ELK3 regulated cell migration capacity, which could have a direct impact on mCRPC. Collectively, these findings shed light on the underlying transcriptional mechanisms driving Abi response, demonstrating that TraRe is a promising tool for generating novel hypotheses based on identified transcriptional network disruptions. Significance: The computational method TraRe built on Bayesian machine learning models for investigating transcriptional network structures shows that disruption of ELK3, MXD1, and MYB signaling cascades impacts abiraterone resistance in prostate cancer.